Efficacy of Vigabatrin With High Dose Prednisolone Combination Therapy Versus Vigabatrin Alone for Infantile Spasm: a Randomized Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 250
- 试验地点
- 1
- 主要终点
- Cessation of spasms
研究概览
简要总结
Infantile spasms (IS) are seizures associated with a severe infantile epileptic encephalopathy. Both cessation of spasms and electrographic response are necessary for the best neurodevelopmental outcomes. Adrenocorticotrophic hormone (ACTH), or prednisolone, or vigabatrin are considered the first-line treatment individually. However, ACTH expense and availability are the barriers in developing countries including Thailand. Vigabatrin, therefore, is the first recommended by Epilepsy Society of Thailand due to ACTH unavailability. Recently, combined steroid treatments (either ACTH or high dose prednisolone) with vigabatrin are superior in cessation of spasms compared to steroid treatment alone. Thus, this study is aimed to compare the efficacy of vigabatrin with high dose prednisolone combination therapy and vigabatrin alone.
详细描述
Infantile spasms are recognized as epileptic encephalopathy which include the hypsarrhythmia or variants electroencephalographic (EEG) features and psychomotor regression. Various underlying conditions are associated with the infantile spasm included cerebral malformation, hypoxic ischemic encephalopathy, genetic disorders (Down syndrome), tuberous sclerosis complex (TSC), etc. Although vigabatrin has the evidence to use as the first line treatment for infantile spasm related with TSC. Adrenocorticotrophic hormone (ACTH), or high dose prednisolone, or vigabatrin are the first line treatment of IS in non-TSC.
The effectiveness of ACTH versus high dose prednisolone question have not yet definitely answered. Furthermore, ACTH expense and availability are the barriers in developing countries including Thailand. Vigabatrin, therefore, is the first option of therapy recommended by Epilepsy Society of Thailand due to ACTH unavailability. Recently, combined steroid treatments (either ACTH or high dose prednisolone) with vigabatrin are superior in cessation of spasms compared to steroid treatment alone. Questions about the clinical cessation of IS and electrographic remission by combination treatment with vigabatrin and high dose prednisolone compare to vigabatrin alone have not fully elucidated. Thus, this study is aimed to compare the efficacy of vigabatrin with high dose prednisolone combination therapy and vigabatrin alone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Investigator, Outcomes Assessor)
盲法说明
Each patient will visit the clinic at Day 8, 14, 43, and 3 months by outcome assessor who is blinded for treatment to determine seizure frequency and adverse events. Those patients will be seen and under taking care of primary neurologists and pharmacists who are not blinded to treatment at the same visit as a standard clinical practice and check with compliance and adjust vigabatrin or prednisolone following each treatment allocated (if needed). Family or caregivers will not be blinded to treatment. EEG will be scored using BASED scores at Day 0 (before treatment), 14, and 43 to assess the resolution of hypsarrhythmia.
入排标准
- 年龄范围
- 2 Months 至 14 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age at 2-14 months at date of enrollment
- •Clinical diagnosis of infantile spasm assessed by pediatric neurologist and hypsarrhythmic pattern or variants interpreted by pediatric epileptologist
- •Thai nationality
排除标准
- •Previous treatment (within the last 28 days) with vigabatrin or corticosteroid
- •Previous diagnosis of epileptic encephalopathy e.g. early infantile epileptic encephalopathy and early myoclonic epileptic encephalopathy
- •Has a clinical suspicious or diagnosis of tuberous sclerosis complex characterized by one of these; known affected parent, previously diagnosed cardiac rhabdomyoma, hypomelanotic macules, forehead fibrous plaque, shagreen patch, retinal phakoma, or known polycystic kidneys
- •A contraindication to vigabatrin or corticosteroid such as recent varicella or herpes zoster infection, gastrointestinal hemorrhage etc.
- •Thai language ability of the parents or guardians is that they may not understand what is being requested of them.
- •Predictable lack of availability of follow up
研究组 & 干预措施
Combination therapy with vigabatrin and prednisolone
Vigabatrin (tablet of 500 mg) dose based on weight divided in two times. The protocol for vigabatrin dose is 50 mg/kg/day at Day 1, 100 mg/kg/day at Day 2, and increase to 150 mg/kg/day if seizures still occur after 72 hours after treatment. Vigabatrin will be continued for 3 months, then reduced and completely off within 4 weeks.
Prednisolone (tablet of 5 mg), 40 mg of prednisolone (10 mg oral 4 times a day) for 14 days. Prednisolone will be increased to 60 mg/day (20 mg oral 3 times a day) if seizures still occur at Day 7 or recur within Day 8 - 14. Then, prednisolone will be reduced every 5 day until completely off within 1 month. Total prednisolone duration is 1 month.
干预措施: Combination therapy with vigabatrin and prednisolone (Drug)
Vigabatrin alone
Vigabatrin (500 mg/tab) dose will be calculated on weight basis divided in two times. The protocol for vigabatrin dose is 50 mg/kg/day at Day 1, 100 mg/kg/day at Day 2, and increase to 150 mg/kg/day if seizures still occur after 72 hours after treatment.
Vigabatrin will be continued for 3 months, then reduced and completely off within 4 weeks.
干预措施: Vigabatrin Tablets (Drug)
结局指标
主要结局
Cessation of spasms
时间窗: Assessed during Day 14 to Day 42 after treatment.
Defined as no witnessed spasms (either clusters or single spasms) from Day 14 to Day 42 inclusive.
次要结局
- Relapse of spasms(Day 42 to 3 months after treatment)
- Electrographic response(Assessed during Day 14 and Day 43 after treatment.)
- Extended electroclinical response(Between Day 42 and Day 49.)
- Epilepsy outcome at age 18 months(From Day 42 to age 18 months)
- The time taken to absence of spasms(Day 1 to Day 14)
- Electroclinical response(Between Day 14 and Day 21.)
- Adverse reactions(Day 1 to Day 14, from Day 15 to Day 42, and from Day 43 to 4 months into the trial)
研究者
Kullasate Sakpichaisakul
Pediatric epileptologist
Queen Sirikit National Institute of Child Health